The embodiments relate to a device and a method for concentrating and detecting cells in flowing media, in particular, marked cells in complex media such as for example blood.
Until now, there has been no non-optical solution for carrying out reliable individual cell detection with a magnetic flow cytometer in laminar flow.
The currently known technical solutions for individual cell detection are predominantly optical methods for detecting cells with fluorescent markers or by scattered light from a suspension in flow channels. Magnetic methods are mainly restricted to concentrating magnetically marked cells, and to biosensors comprising magnetoresistive transducers.
The following magnetic methods are known:                1) Applying an external magnetic field perpendicularly to the flow direction. In a gradient field, it is also possible to a limited extent to sort analytes according to size and magnetic moment, cf. N. Pamme and A. Manz, Anal. Chem., 2004, 76, 7250.        2) Installing a ferromagnetic conductor at the bottom of the separating chamber. Owing to the local field gradient, magnetizable cells are concentrated at the bottom along the ferromagnetic conductor and separated at flow rates of <1 mm/s of unmarked cells, in this respect, see D. W. Inglis, R. Riehn, R. H. Austin and J. C. Sturm, Appl. Phys. Lett., 2004, 85, 5093.        3) A current conductor is fitted at the bottom of the separating chamber. The flow current flow induces a magnetic field which in turn—as mentioned in point 2—can be used to concentrate cells (flow rate: 6 nl/min in microfluidic channels) Pekas, N., Granger, M., Tondra, M., Popple, A. and Porter, M. D, Journal of Magnetism and Magnetic Materials, 293, pp. 584-588, (2005). c) M. Tondra, M. Granger, R. Fuerst, M. Porter, C. Nordman, J. Taylor, and S. Akou, IEEE Transactions on Magnetics 37, (2001), pp. 2621-2623.        
The detection of marked cells with embedded GMR sensors can to date be carried out only statically in analogy with an assay, and not dynamically i.e. for example in laminar flow. Cf: J. Schotter, P. B. Kamp, A. Becker, A. Puhler, G. Reiss and H. Brückl, Biosens. Bioelectron., 2004, 19, 1149.
Commercial manufacturers of sensors having magnetoresistive elements only offer assays for DNA and protein analysis for in vitro diagnosis. In this regard, reference may for example be made to the Internet addresses of magnabiosciences.com, diagnsticbiosensors.com, seahawkbio.com and san.rr.com/magnesensors.
In known magnetic flow cytometers, cells which are marked with magnetic markers, for example superparamagnetic labels, are transported in a flow chamber near the surface over a magnetoresistive sensor (for example a GMR (giant magnetoresistance sensor), as described for example by N. Pekas, M. D. Porter, M. Tondra, A. Popple and A. Jander, Appl. Phys. Lett., 2004, 85, 4783.
A problem with this is that the required proximity of the marked cell to the sensor is not achieved, as the leakage magnetic scattered field due to the magnetic markers decays with the third power of the distance from the sensor. With the previously known methods, it is therefore generally far from possible to detect all the marked cells.